N-(6-F-18-fluorohexyl)-N-methylpropargylamine: A fluorine-18-labeled monoamine oxidase B inhibitor for potential use in PET studies

We have synthesized N-(6-F-18-fluorohexyl)-N-methylpropargylamine (F-18-FHM P) as a positron emission tomography (PET) radiotracer for monoamine oxidas e B (MAO-B). The radiosynthesis was carried out by a fluorine for-bromine s ubstitution in 30-40%; radiochemical yield in specific activities of 1-2 Ci /mu mol. Selectivity for MAO-B was demonstrated by the high affinity of (R) deprenyl (IC50 = 6.8 nhl) and lower affinity of clorgyline (IC50 = 1.2 mu M) for the inhibition of F-18-FHMP binding in vitro in rat brain homogenate s. In vitro autoradiographic studies in rat brain slices showed localizatio n of F-18-FHMP in regions such as the ependyma of the lateral ventricle, do rsal raphe, area postrema, and other regions such as the cerebellum. The sp ecific binding observed in the autoradiograms was displaced by preincubatio n with (R)-deprenyl. In in vivo experiments, the uptake of F-18-FHMP in the rat brains was high (0.10-0.20% injected dose/g). The binding of F-18-FHMP in the rat brain correlated with the general distribution of MAO-B and was displaced completely by preadministration of 10 mu M (R) deprenyl. These r esults suggest that F-18-FHMP is a potential PET radiotracer for MAO-B for use in in vitro and in vivo experiments. NUCL MED BIOL 26;1:111-116, 1999. (C) 1998 Elsevier Science Inc.